Project Summary (Abstract) Improving cognitive function is of critical importance to individual?s wellbeing and daily functioning as cognitive declines are common in healthy aging population and in patients with psychiatric disorders, posing significant financial burden to public healthcare. As a promising intervention that systematically fosters attention and self-control capacities, mindfulness training (MT) has shown evidence of enhancing cognitive function, yet mixed results regarding its cognitive benefits are observed, suggesting more rigorous investigation is needed to comprehensively evaluate the potential of MT in bolstering cognitive function. A thorough examination of previous literature reveals an unclear mechanism of action by which MT exerts its beneficial effects on cognitive function, as most MT studies have examined cognitive function with only few narrowly focused tasks, and without a coherent theoretical framework that can systematically explain potential cognitive improvement and their relation to brain functional changes. Further, the importance of individual difference factors that are likely to moderate or mediate intervention effects has been largely neglected by previous research, adding another source of ambiguity to the existing literature. The current project aims to address these critical research gaps in order to accurately evaluate MT effects on cognitive function and their neural mechanisms, while considering the role of individual differences in influencing intervention effectiveness. Thus, Aim 1 will exploit novel and advanced network neuroscience approaches to investigate the neural mechanisms of MT at the level of large-scale brain networks, since the intervention can be construed as ?attention state? training that induces state-related changes, which may be best captured at the level of functional networks, instead of isolated regions. Aim 2 will rigorously examine cognitive effects of MT with a more comprehensive and theoretically-targeted task battery developed based on existing cognitive control framework and will also investigate whether individual differences in trait measures of mindfulness could influence the magnitude of cognitive improvement. Aim 3 will test whether the extent of alteration in brain network integration will predict the magnitude of training-related improvement in cognitive function, strengthening the mechanistic link between MT effects on brain function and behavior. The project will involve a powerful discordant twin and longitudinal design, which will be the first MT study that utilizes such a design, in order to reduce potentially confounding control-group differences (monozygotic twins share the same genes) and allow for stronger causal inferences on the mechanisms and effects of MT than in previous studies that used poorly matched controls or no controls. The results of this project will have far-reaching impacts on the development and optimization of MT to further bolster its benefits, and on the implementation of such intervention in populations with deficits in cognitive function.